Process for producing salicylic-acid-menthol ether.



UNITED STATES PATIENT OFFICE.

BERTRAND BIBUS AND-RUDOLF scHEUBLE, or VIENNA, AUSTRIA, HUNGARY.

' PRocEss .-FoR PRODUCING SALIOYLlC-AQlD-MENTHOL ETHER.

Application filed May 13. 1905.

To all whom it may concern.-

Be it known that We, BERTR'AND BIBUS and RunoLF' HEUBLE, subjects of theEmperor of Austrla-Hungary, and'residents of Vienna,

AustriaHungary, have invented certain new.

salicylic-acid-menthol ether, so that the theoretically possible yieldof the finished product may be very nearly attained.

To this end the process of our invention consists in mixin menthol andsalicylic acid in quantities slightly in excess of the ratio of theirmolecular weights and heating the mixture. A current ofsuitably-reacting dry gas is thereupon injected into and blown throughthe heated mixture for purposes of removing the water-vapors formed bythe combination of salicylic acid and menthol, said combinationproceeding directly with elimination of .one molecule of water for everymolecule of salicylic-acid menthol ether formed. Said current of gas canbe advantageously employed as an aid in heating the mixture. If

utilized in this way, it is essential'that the temperature of said gasbe controlled and regulated so that a degree of heat somewhat in excessof the melting-point of the reaction mixture, and yet never higher than220 centigrade, is maintained. The yarious reactions taking place by thehereinbefore-described process result in the formation ofsalicylic-acid-menthol ether. Various other compounds. and by-productsexist in the reaction mixture, these being small quantities solvents,but insoluble in Water.

of uncombined salicylic acid and menthol, menthene, and menthylcompounds. The isolation and purification of the desired ether can beeffected by any of the well-known chemical manipulations, the mostpreferable of these .being fractional distillation. The resultingcompound is a colorless odorless thick oily liquidsoluble in mostorganic Under a Letters Patent. Patented Sept. 4, 1906. Serial at.260,861. (Specimens) compound is capable of distillation in cacao.Saponification of the material results in pure menthol and salicylicacid, respectively.

The material is of particular value as a medicinal or pharmaceuticalpreparation and finds some application in the arts and in technicalWork.

According to our invention the prepara tion of the material ispreferably realized according, to the manipulations and propor tionshereinafter stated. Thirty (30) parts of mentholand one hundred andforty (140) parts of salicylic acid are heated to a temperature of from140? to 220 centigrade by means of an oil-bath. Gaseous reagents,preferably either hydrogen, carbon dioxid, or hydrochlorlc-acid gas,advantageously heat ed to a temperature Within the limits previouslystated are injected into and blown through the mixture. 1 A perfectlyquiet and harmless reaction takes place, the same re sultin and thementhol in molecular proportions. The reaction mixture is, if necessary,diluted with either ether, petrol, petroleum-ether, or-

any equivalent and similar organic solvent and unaltered salicylic acidpresent, because of an excess of this reagent purposely added at thebeginning of the process is neutralized by decomposition with an aqueoussolution of an alkali-metal carbonate or bicarbonate. Such treatmentprepares the reaction mixture for a fractional distillation conductedunder reduced pressure and, if necessary, with steam under ressure, theresult of such distillation beim p henol, menthol, menthene,

and, if hydrochloric acid-gas has been employed, as hereinbefore stated,menthyl chlorid and a fraction of salicylic acid-menthol ether. Theseproducts pass off in the order mentioned, respectively.

By cawfully-conducted fractionation salicylic-acid-menthol etherc'an besecured in an absolutely pure state-that is, the desired product resultsfrom this operation if the fraction temperatures are closely watched.

' An important feature of our invention is the utilization of theby-products of the hereinbeforemientioned process for the produc tion ofadditional quantities of the other desired, and it is due to theutilization of these byproducts,'as hereinafter described, that a yieldof ether approximating the one theoretpressure often millimeterssalicylic-acid-mem thol ether boils at 175 centigrade. The

ically possible can be attained. To this end in the combination ofsalicylic acid the distiliates-that is, the "by-products resuit ng fromthe fractionation of the salicylic acid-menthol etherare freed fromphenol by either neutralization with a chemical of the alkali class orby a subsequent carefully-6on ducted fractional distillation.Neutralization with an alkali-401* example, with sodium or potassiumhydroKidis preferred. Menthol, menthene, and, dependent upon whether ornot hydrochloric acid gas has been-pre-v viously employed, menth *1chlorid' entirely freed from phenol result. The treatment of suchmenthol, menthene, and mentholchlorid. with hydrochloric acid suitablyappliedurb der increased pressure results in a uniform mixture ofmenthyl chlorid. A substitution reaction between this menthyl chloridand any metallic salicylate sodium salicylate, for exampleresults insalicylic-aciimentho l ether and the chlorid of the metal lidded.metaliic salicylate. The use of sodium salin ylate for the step of theby-product process will therefore yield the salicylic-zicid-mentholether and sodium chlorid. The salicylicaoid-menthol ether may be securedprecisely as in the direct production of the ether-yin, bycarefully-conducted fractional distillation: The herefrom-resultingcompound is identical with the product of the direct processhereinbefore described.

The quantity of salicylic acid menthol ether secured from theherein-described diroot and by-product processes is very nearly theequivalent of the theoretical yield possible from calculated initialquantities of salicylic acid and menthol.

It will be apparent that other gases than those hereinbeiore mentionednamely, hydrogen, carbon dioxid, and hydrochloric-acid gaswill performthe functions of a dehydrating agent necessary for the success of thecombining reaction between salicylic acid and menthol, and it Will-beunderstood that such gases come within the scope of this iiivention. Itwill, furthermore, be apparent that the hydrochloric-acid reagentemployed for the production of menthyl chlorid in the by-product processcan be successfully re placed by any of the halogen compounds ofhydrogen, these being hydrogen iodid, hy drogen fluorid, hydrogenbromid, and that therefore these reagents also come Within the scope ofour invention.

To claim i. The hereiu-described process of producingsalicylic-scid-menthol ether, consisting in heating salicylic acid andmenthol to effect combination of said materials in molecularproportions, in dehydrating the reaction mixture with gaseous reagents,in neutrali said reaction mixturewith carbonic-acid sal of the alkalimetals, and in fractionally distilling the resulting mixture therebyseparating the salicylic-scid-menthol-ether fractionirom other portionsof the distillate:

2. The he'rein-desc'ribed process of pirodu'c saliicylic-acid-mentholether, consisting in salicyclic acid'and menthol to effect mentholether-fraction from other portions of the distillate.

e. The-herein-descrihed process of producing salicylic-acid-mentholether, consisting in heating salicylic acid and menthol theeiiectcombination of said materials in molednlar proportions, in dehydratingthe reaction mhrture with gaseous reagents, in neutralizing saidreaction mixture With carbonic-acid salts of the alkali metals, infractionally' distilling theres'ulting mixture thereby separating thesalicylic-acid-menthol-ether fraction from other portions of thedistillate and in neutralizing the phenol of said distillate with alkalireagents.

5. The herein-described process of producing salicylic-acid-mentholether, consisting in heating salicylic acid and menthol to effectcombination of said hi Lterrals m molecular proportions, in dehydratingthe reaction mixture with gaseous reagents, in neutralizing saidreaction mixture With carbonic-acid salts of the alkali metals, infractionally distilling the resulting mixture thereby separating thesalicylic-acid-menthol-ether fraction from other portions of thedistillate and in neutralizing the phenol of said distillate with sodiumhydroxid.

6. The herein-described process of producing salicylic-acid-mentholether, consisting in heating salicylic acid and menthol to effectcombination of said materials in molecular proportions, in dehydratingthe reaction mixture with gaseous reagents, in neutralizing saidreaction mixture with carbonic-acid salts of the alkali metals, infractionally (lit titling the resulting mixture thereby separatingthe'salicylic-acid-menthol-ether fraction from other portions of thedistillate, in neutralizing the phenol of said distillate with alkalireagents, and in treating with halogen compounds of hydrogen.

7. ing salicylicacidmen thol ether, consistin in heating salicylic acidand menthol to e ect The herein-described process of produce"combination of said materials in molecular proportions, ,dehydrating thereaction tralizing the phenol of said distillate {r alkali reagents, andin treating ith hydroing t mixture with gaseous reagents, in neutralizinsaid reaction mixture with carbonic-acid salts of the alkali metals,in'fractionally distillin the resulting mixture thereby separathesalicylic-acid-menthol-ether fraction from other portions of thedistillate, in 1 cu];

chloric acid.

' 8. The herein-described process oi producv ing salicylic-acidrmentholether, consistin in heating salicylic acid and menthol to effectcombination of, said materials in molecular proportions, dehydrating thereaction ing t tralizing the phenol of said distillate with alkalireagents, in treating with halo en compounds of hydrogen, and inaddition of a metallic salicylate.

, i 9. The herein-described process of producing salicylicacid-mentholether,consistin in heating salicylic acid and menthol to'eect combination of said materials in molecular proportions xindehydrating the reaction mixturewith gaseous reagents, in neutraliz ingsaid reaction mixture with carbonic-acid salts of the alkali metals, infractionally distillin the resulting mixture thereby separating thesalicylic-acidmenthol-ether fraction from other portions of thedistillate, in neutralizing the phenol of said distillate withalkali reaents, in treating with halogen compounds 0? hydrogen, and in addition ofsodi um salicylate.

10. The herein-described process of producing salicylic-acid-mentholether, consisting in heating salicylic acid and menthol to effectcombination of said materials in molecular proportions, in dehydratingthe reaction mixture with gaseous reagents, in neutralizing saidreaction mixture with carbonicacid salts ;of the alkali metals, infractionally distillin the resulting mixture thereby separatin thesahcylic-acid-menthol-ether fraction trom other portions of thedistillate, in neutralizing the phenol of said distillate with alkalirea ents, in treating with halogen compounds oi hydrogen, in addition ofa metallic salicylate, and in fractionally distilling the reactionmixture thereby separating the salicylic-acid-merithol-ether fraction.

In testimony whereof we afiix our sigma-- tures in presence of twowitnesses.

BERTRAN BiBUs. RUDOLF CHEUBLE.

Witnesses:

IFUR FUoHs, ALvEsTo S. HoeUE.

